Combining Particle Engineering with Device Development to fine tune DPI performance of AP301

Isabel S.Lopes , Bernhard Fisher, Hendrik Fisher, João V. Fernandes, Pedro Serôdio, Filipe Neves

AP301 is a new synthetic peptide designed for the treatment of pulmonary lung oedema through the activation of the ENaC channel of type II alveolar cells of the lungs. This product was already administered clinically in the form of a nebulized version, with very promising results in the treatment of patients suffering from Acute Respiratory Distress Syndrome and with primary graft dysfunction following lung transplantation. In order to further expand the range of applications for this product, and given that nebulization is not the preferred delivery route for the vast majority of at home patients, a dry powder inhalation platform was attempted for this product.
For that purpose a spray drying (SD) process was developed in order to produce different Drug Alone powders targeting different Particle Size Distributions (PSD). The objective was to manipulate this property of the powder in order to reduce cohesive / adhesive forces and thus to increase the aerodynamic performance. Throughout the program it was demonstrated that the SD process enabled obtaining stable materials, within the targeted PSD and with a high degree of purity and bioactivity.
Due to the rescue nature of the treatment in some of the intended applications, and due to the difficulty of handling capsule-based devices in emergency situations, the need for patients to have a highly portable and easy to use disposable device was identified. For this reason, a device development program was conducted, targeting the development of an enhanced version of the currently marketed single dose disposable device TwinCaps®, able to accommodate large payloads of spray dried powder. Prototypes of this device and one off the shelf device were used to determine the aerodynamic performance (APSD) of the produced powders. The results indicated the feasibility of obtaining high emitted and fine particle dosages for drug alone powders of AP301, with both types of devices, and that this performance remained stable throughout a 3 month period at different storage conditions (25ºC/60%RH and 40ºC/75%RH).

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